Hello,

In my first post, I mentioned that I am currently conducting a new series of tests, Series 4. Here I will explain what I am doing and why. I hope to be able to post some preliminary results in a few weeks.

As described in detail on my web site, I have already confirmed that total serum B12 is useless for the diagnosis of vitamin B12 deficiency. My claim is supported by the opinion of experts quoted on my web site:

• Read the quotes in Expert Opinion under Vitamin B12 Deficiency
• Read at least reference G1, Vitamin B12 Deficiency, Oh and Brown, Am Fam Physician
• Read reference H6, Active-B12 (holotranscobalamin)

My own findings, from my tests of 2006, support this claim:

• Read My Story under The Investigation

Before I continue, I should point out that what I am doing is potentially very dangerous. As they say, "please don't try this at home". I am working closely with my doctors and pathology labs to minimise the risk.

I am currently using myself as a "guinea pig" to determine the effectiveness of the various pathology blood tests. I am doing this by allowing my vitamin B12 level to progress from depletion of stores to definite cellular B12 deficiency.

If you would like some information about the stages of vitamin B12 deficiency then I suggest that you read page 16 of reference H6, and reference G1. There are direct links to these reports from the References page of my web site.

Unlike the first three series of tests, described in detail on my web site, this new series is not investigating the specific laboratories taking part. The labs are fully cooperating with my investigations.

There are two objectives of my current research:

• Determine the minimum dose needed to correct my B12 deficiency
• Evaluate the effectiveness of the currently available pathology tests

I commenced having my blood samples collected weekly since 5 March 2007, by QML Pathology in Brisbane, as part of a dose-finding trial. This has been done by commercial agreement, at my expense, and no cost to Medicare.

The weekly sample was only tested for total serum B12 by QML, until we added holotranscobalamin (Active B12) on 17 September.

To protect myself against the onset of vitamin B12 deficiency, which might not be detected by either total serum B12 or Active B12, I also tested for the two metabolic markers of B12 deficiency. Every four weeks, QML sends three frozen serum samples to the NSW Biochemical Genetics Service at The Children's Hospital Westmead in Sydney (CHW). One of these samples is tested for methylmalonic acid (MMA) and total homocysteine (tHcy) using stable isotope dilution tandem mass spectrometry (LC-MS/MS); this is the reference method used by Mayo labs. All three samples are stored frozen for future testing by another lab. I have confidence in the reliability of results from CHW because of their excellent performance last year.

The initial main objective was to assist in finding the cause of the deficiency. For example, if the required dose was very small then the cause is more likely to be dietary deficiency than PA. By slowly reducing the dose of oral B12 in steps, from 1000µg per day to 10µg per day, I can test the dose response. I have used Excel to construct charts to compare the dose and the response.

I recently decided to extend the trial to include the second objective of observing the response of all four analytes, total serum B12, active B12, MMA and tHcy, as my cellular vitamin B12 deficiency proceeds.

When my results are conclusive, or when it becomes too dangerous to continue, I will commence increasing the dose of oral B12 in steps up to 2000µg per day.

I intend to publish preliminary results on my web site, as charts and a table, once the trend is clearer. It has taken eight months, and 35 blood tests, so far. Clinical trials take a long time and cannot be hurried if we are to obtain valid data.

To summarise, these are the tests that I am comparing as markers of vitamin B12 deficiency:

• Total serum B12
• Active B12 (holotranscobalamin)
• Methylmalonic acid
• Total homocysteine

Please post any comments or questions to this thread. If you wish to contact me for a private discussion, please Email me from Paul in the Contact page of my web site at http://www.paulgolding.id.au/.

Thank you.

Paul